Obesity/overnutrition in humans makes a major contribution to increased morbidity of chronic diseases such as diabetes, coronary heart disease, some types of cancer, and hypertension, and is associated with increased mortality. Over the past few years, NIH has funded at least 14 separate longevity studies (plus/minus food restriction) using relatively lean rodent models such as Fischer 344 and Sprague-Dawley rats. However, few studies of aging have been done using genetically obese rodents which have otherwise been well characterized with respect to their metabolic and behavioral abnormalities. This, in part may reflect the lack of availability of large numbers of specific pathogen free (SPF) genetically obese animal models to do well controlled studies. Carefully designed studies of obesity and aging are critical to laying a sound foundation for future mechanistic studies of aging and genetic obesity at the cellular and subcellular level. This proposal will test a series of five hypotheses related to genetic obesity, gender, and aging. These hypotheses will be tested using a well studied animal model of obesity, the Zucker fatty rat (fafa) that is hyperphagic, hyperinsulinemic and insulin resistant, but not diabetic. Obese groups for each gender pair- fed to lean rats will be included. By using SPF male and female obese and lean rats we will be able to study pathology associated with obesity/gender and not endemic disease that can alter the aging process. Hypothesis #1: Genetic obesity will result in decreased median lifespan and 10th percentile survivorship, and will be related, in part, to the lifetime increase in food intake in obese animals. In conclusion, this animal model should prove to be highly relevant to the human condition since obesity is a major problem in the United States and is associated with increased morbidity and mortality. At UC Davis we have a well established colony of SPF Zucker obese and lean rats. The collective experience of our team in obesity, aging and in methodologies for longevity studies, uniquely suited to carry out critical experiments and offers an unparalled opportunity to begin to study the interaction of gender/genetic obesity with the aging process.